Cells: The body’s ultimate sports car

Anand Asthagiri, associate professor of chemical engineering, has developed a method for driving cells from Point A to Point B with more precision than ever. Above, the movement of human mammary epithelial cells is imaged by time-lapse microscopy using an inverted Zeiss Axiovert microscope.

Anand Astha­giri can think of sev­eral rea­sons why a sci­en­tist would want to get behind the wheel of a cell — which he calls the “ulti­mate dri­ving machine.” Having the ability to move a cell from Point A to Point B, he said, could rev­o­lu­tionize tissue engi­neering and trans­form the under­standing of var­ious dis­eases, including cancer.

“It’s a com­plex problem, but I think we can make headway on it if we think about the cell as an engi­neer­able entity,” said Astha­giri, an asso­ciate pro­fessor of chem­ical engi­neering in North­eastern University’s Col­lege of Engi­neering.

In a paper pub­lished in Feb­ruary in the journal Lang­muir, Astha­giri and post­doc­toral researcher Kei­ichiro Kushiro present a simple means of designing “traffic pat­terns” to guide cell move­ment.

Astha­giri said one way cells can be encour­aged to move in a par­tic­ular direc­tion occurs nat­u­rally in our body — for instance, when our immune system responds to attacks. In a process called chemo­taxis, cells move across a gra­dient of attrac­tant mol­e­cules, from areas of lower to higher concentration.

Cells move by sticking and crawling on an adhe­sive sur­face using a variety of reg­u­la­tory mol­e­cules, Astha­giri said. “If the sur­face is uni­formly adhe­sive, then they’ll just move ran­domly,” he explained. “If you present them in a gra­dient of chemoat­trac­tant, they’ll move toward the chemoat­trac­tant but you won’t get the fine con­trol of where they go.”

“Fine con­trol” inter­ested Astha­giri and Kushiro. In pre­vious work, the researchers defined a set of micro-​​patterns that could con­strain the move­ment of cells over an adhe­sive sur­face. A stripe of adhe­sive mol­e­cules, for example, keeps cells moving within that area. A teardrop shaped pat­tern — which looks like a migrating cell — gives them direc­tion­ality, moving toward the broad end and away from the narrow end.

This time, the team explored a hybrid of the two micro-​​patterns, inserting a stripe into the teardrop to create a spear shape. They aligned these adhe­sive spears in a track-​​like square and then let the cells wander. While Astha­giri expected the cells to move around the track with direc­tion­ality and increased speed, he did not expect enhanced directionality.

“You put this piece in the middle that has no ability to endow direc­tional bias but yet it does, so there’s clearly more going on in this hybrid,” Astha­giri explained. When cells are exposed to the stripe longer, they are more likely to turn despite the fact that stripes do not inher­ently pro­mote turning.

Astha­giri and Kushiro are cur­rently inves­ti­gating why the com­bi­na­tion of the two shapes makes for a more con­trol­lable system. They are also set­ting up “traffic pat­terns” made up of stripes, teardrops and spears to explore ways in which the method can be tuned to cause more directed cell movements.

“We are excited by this because it opens two very inter­esting avenues of oppor­tu­nity,” Astha­giri said. “One avenue is to learn more about the fun­da­men­tals of how cells move and exploit it. The other exciting pos­si­bility is on the appli­ca­tion side. Could we use this to send some cells one way and other types of cells another?”

If the latter proves true, Astha­giri said, then cancer cells could sep­a­rate them­selves from non­cancerous cells and newly dif­fer­en­ti­ated stem cells could go exactly where they’re needed in a tissue graft.

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